Philadelphia, March 2, 2021 – Introducing the first deep dive into immune system behavior in patients with multisystem inflammatory syndrome in children (MIS-C), researchers at the Children ‘s Hospital of Philadelphia (CHOP) and the Perelman School of Medicine at the University of Pennsylvania have found that children with this condition have highly active immune systems that are, in many ways, more similar to those of adults with COVID-19. The results, published today in Psychology of science, demonstrating that a better understanding of immune activity in patients with MIS-C could not only help in the better treatment of these patients but also improve treatment for adults with severe COVID-19 .
“This study shows that children with MIS-C are highly immune-mediated, especially when it comes to CD8 T cells, but that this activation spawns once patients begins to improve clinically, “said Laura Vella, MD, PhD, attending physician in the Department of Infectious Diseases at CHOP and the first author of the study. “Our findings provide a broad immunologic basis for understanding pathogenesis and recovery in this novel SARS-CoV-2 associated inflammatory syndrome, with potential side effects for disease. adult. “
Pediatricians first recognized MIS-C in April 2020, when pediatric patients began to appear with symptoms including hypertension, including fever, gastrointestinal distress, and cardiogenic shock. The syndrome, which is thought to be a post-infectious complication of SARS-CoV-2 disease, is similar in clinical manifestation to Kawasaki disease, primarily vascular involvement, but differs from Kawasaki disease in major ways, including specific clinical, inflammatory, and autoantibody signatures. The syndrome also lacks the respiratory problems that are common in COVID-19 adult and pediatric patients. However, to date, the immunologic factors driving MIS-C were not well understood.
To better understand the immunology behind MIS-C, the researchers collected blood samples from patients admitted to CHOP with COVID-19 or MIS-C between April and June 2020. They analyzed more than 200 immune parameters, including serologic and plasma cytokine data, and compared these data with samples from adult COVID-19 patients, received adult COVID-19 subjects, and healthy adults .
The researchers found that children with MIS-C had high T cells, specifically CD8 T cells and a highly involved CD8 T mobile cell subset. These immune-sensitive CD8 T cells have a suggested role in controlling viral infection or reactivation and have also been implicated in cardiovascular disease, which may be related to the viral symptoms observed in these patients. The researchers found patients with MIS-C, who had high CD8 T secretory cells, also needed vasoactive support, increased D-dimer, and decreased platelets. CD8 T cell proliferation was significantly higher than that observed by the researchers in pediatric patients with COVID-19 starvation and most adults with COVID-19, but the level of CD8 T cells in MIS patients fell. -C in conjunction with clinical development.
The study also identified a skewed B cell response in patients with MIS-C compared with pediatric hungry COVID-19 and reconstituted adult disease. Patients with MIS-C are virtually all-seropositive for SARS-CoV-2, meaning that sufficient time had elapsed since infection for antiviral antibody was developed and detected. Pediatric and adult patients with seropositive-induced COVID-19 were inconsistent, consistent with the notion that MIS-C is a delayed event after SARS-CoV-2 infection. But despite the fact that MIS-C was a delayed event, the researchers found that MIS-C patients had elevated plasmablasts, or non-proliferated B plasma cells, whereas plasmablasts in adults who overcoming COVID-19 returns to baseline two or three weeks after symptoms resolve, although a subset of hospitalized adult patients with COVID-19 had a stable increase of plasmablasts.
The researchers suggested three potential drivers of the immune pathogenesis in MIS-C: (1) continuous activation of altered immune responses, directed by sequencing of SARS-CoV-2 antigen; (2) additional stimulation, such as the virus entering a new strain type or secondary infection, occurs two to three weeks after the first infection with SARS-CoV-2; or (3) a self-defense response. More research is needed to study these situations.
“SARS-CoV2 disease can lead to a broad spectrum of clinical and immunological outcomes,” said E. John Wherry, PhD, Director of the Institute for Psychology and senior author of the study. “Not only did the use of the‘ Immune Health ’accounting approach for pediatric COVID-19 patients identify specific features of the MIS-C pediatric presentation of the disease, but the insights gained from examining MIS patients could -C Emerging new therapeutic opportunities for pediatric and adult COVID-19 patients. “
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The research received support from the National Institutes of Health, as well as a COVID-19 research award at the University of Pennsylvania’s Glick Institute of Psychology, Allen Institute for Immunology, Mark Foundation Research Foundation, Leukemia and Lymphoma Foundation, Alex’s Lemonade Stand Foundation for Cancer childhood, and the Chop Borders Program Immunity Dysregulation Team.
Vella et al. “Deep Immune Profile of MIS-C shows marked but immobilized immune activity compared to adult and pediatric COVID-19,” Psychology of science, online March 2, 2021, DOI: 10.1126 / sciimmunol.abf7570
About Philadelphia Children’s Hospital:
Philadelphia Children ‘s Hospital was founded in 1855 as the first pediatric hospital in the country. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and launching major research initiatives, the Children’s Hospital has found much to discover. a discovery that has benefited children all over the world. Its pediatric research program is among the largest in the country. In addition, the unique family-based public care and service programs have recognized 595-bed hospitals as a prime candidate for children and adolescents. For more information, visit http: // www.
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